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Jesper Juel Mauritzen:
Regulation of virulence properties in the fish pathogen Vibrio anguillarum: The role of prophages and quorum sensing

Date: 02-05-2022    Supervisor: Mathias Middelboe




Vibrio anguillarum is a marine fish pathogenic bacterium that causes vibriosis in many fish species leading to large economic losses in the aquaculture industry. Yet, the factors governing the pathogenicity in this bacterium are largely unknown. Many bacterial pathogens can communicate to coordinate their virulence program through the process quorum sensing (QS) that relies on the production, release, and detection of signal molecules. At high cell densities, when the signal concentration is high, bacteria activate QS regulation in response to cell density. Here, I uncover the QS regulation in two V. anguillarum isolates and reveal a plethora of genes under QS control, including central processes such as metabolism and virulence. Remarkably, the isolate-specific differences in both the activation and the extent of QS regulation were reflected in their virulence in a fish infection model, adding to our understanding of the mechanisms underlying strain-specific differences in virulence.

Viruses that infect bacteria (phages) can form latent infections, where phage genomes reside dormant in host cells as part of their chromosome (prophages) until induced to multiply and kill their host cells. QS represses this switch from latent prophage to cell lysis. Specifically, the master regulator of QS in V. anguillarum, VanT, binds the phage genome and represses a phage-encoded regulator that plays a part in prophage induction. This highlights a refined use of QS by the host cells to control prophage induction that is clearly distinct from a simple evolutionary arms-race.

Moreover, this thesis reveals a new family of non-tailed NO16-like phages, that are present as prophages inside the genomes of at least 30 species of Vibrio and widely distributed across geographical regions. The pervasiveness of these prophages in V. anguillarum genomes indicates efficient dispersal and underlines that phage-host interactions may often be mutualistic rather than parasitic and drive microbial evolution. In support of this, prophage-containing isolates were more virulent toward a fish model compared to prophage-free isolates, underlining that phage infections can modify virulence of V. anguillarum. Altogether this thesis provides novel insight into the role of QS and prophages for the virulence of the important fish pathogen V. anguillarum, and sheds light on the mechanisms of how QS control prophage induction.